This invention relates to calixarenes and related compounds immobilized onto the surface of a substrate and to a novel method for the production of such products. The substrate may be silica or another inorganic oxide substrate.
Calixarenes are cyclic oligomers of phenol and substituted phenols with formaldehyde, and are characterized by the general structure 
in which n is a value of 3-16, preferably 3 or an even number, most preferably 3, 4, 6 or 8. General information about such molecules can be found, for example in Bauer et al., JACS 107, 6053 (1985) and the texts “Calixarenes” by C. David Gutsche, which is part of the Monographs in Supramolecular Chemistry (J. Fraser Stoddart, ed.; Royal Society of Chemistry, 1989) and “Calixarenes Revisited” by the same author (1998).
Calixarenes are in the form of a cyclical oligomer having a “basket” shape, where the cavity can serve as a binding site for numerous guest species, including ions and molecules. The group R may be hydrogen, or may be any of a number of functional groups including alkyl, alkenyl, alkynyl, allyl, aryl, heteroaryl, alcohol, sulfonic acid, phosphine, phosphonate, phosphonic acid, thiol, ketone, aldehyde, ester, ether, amine, quaternary ammonium, imine, amide, imide, imido, nitro, carboxylic acid, disulfide, carbonate, isocyanate, carbodiimide, carboalkoxy, carbamate, acetal, ketal, boronate, cyanohydrin, hydrazone, oxime, oxazole, oxazoline, oxalane, hydrazide, enamine, sulfone, sulfide, sulfenyl and halogen. Substituent R typically represents a single substituent at the position para to the hydroxyl group. However, the class of calixarene compounds as known in the art includes calix[n]resorcinarenes, which comprise resorcinol moieties that are joined to each other, and typically possess phenoxy groups in a different arrangement around the ring.
Other substances exist that have structures analogous to calixarenes, but which, for example include phenolic groups having bridging moieties other than the methylene bridges shown above in the calixarene structure. These include thiacalixarenes, azacalixarenes, silicacalixarenes and oxacalixarenes, in which some or all of the phenols are bridged by sulfur, nitrogen, silicon and oxygen, respectfully, and calixarenes in which some or all phenol groups are linked by C2 and larger groups, for example by cyclobutyl. Some other types of analogues of calixarenes have been synthesized with a metal atom such as platinum as the spacer bridging phenols [Rauter et al., J Am. Chem. Soc. 116, 616 (1994)]. Other analogous compounds are discussed below. These types of compounds, and others, as known in the art, are referred to here as “calixarene-related compounds”.
There has been much interest in using calixarenes and related compounds as designable hosts for the specific adsorption of small molecule guests. Although protic solvents such as water and alcohols offer an optimum environment for host-guest interactions in this case, calixarenes have generally poor solubility in these solvents, which has required the use of organic solvents in studies of adsorption. However, use of these solvents tends to result in relatively weak binding. Immobilization of calixarenes and related compounds offers a route to circumvent host solubility limitations, but thus far it has required rather laborious syntheses of calixarene derivatives that contain reactive functional groups for polymerization to a surface (e.g. capable of sol-gel hydrolysis and condensation) or other type of surface binding (e.g. via a thiol or sulfide for anchoring on a gold surface). These groups are typically linked to the lower rim of the calixarene or other compound via flexible tethers.
Such flexible tethers usually consisted of ether or thioether groups. For example, Healy et al, Anal. Lett. 31 (9), 1543 (1998) produced calixarenes immobilized onto silica particles through dipropylthio linkers. Schierbaum et al., Science 265, 1413 (1994) used dialkylthio linkers to immobilize calixarenes on gold. Friebe et al., J Chromat. Sci. 33, 282 (1995) produced calixarenes immobilized on silica gels through an unspecified hydrophilic spacer. These tethers, however, tend to decrease the conformational rigidity of the anchored binding site and limit the maximum attainable site density for the calixarenes. Multicavitand complexes that contain stable linkages between a tetrahedral silicon atom and three calixarene phenolic oxygens on the lower rim are known from work reported by Delaigue, et al. Tetrahedron Lett. 1993, 34, 3285-3288, Tetrahedron Lett. 1993, 34, 7561-7564, and Tetrahedron Lett. 1994, 35, 1711-1714. These, however, are free-standing molecules; they are not immobilized onto a substrate.